The role of luteal oestrogen (E2) supplementation for successful embryo implantation in humans awaits further studies. Serum E2 and progesterone (P4) drop to low levels later in the luteal phase of an in vitro fertilization (IVF) cycle resulting in reduced implantation and pregnancy rates, unless hormonal support is provided. The role of E2 in the follicular phase of the menstrual cycle is well established, as it is essential for endometrial priming, but it is also responsible for proliferation of uterine surface epithelium, glands, stroma, and blood vessels. A randomized controlled trial (RCT) in 2006 evaluated the addition of E2 to P4 for luteal phase supplementation in gonadotropin releasing hormone (GnRH) antagonist cycles, as most of the studies had been carried upon GnRH agonist cycles. On the basis of the currently best available evidence, routine use of E2 supplementation during P4 supported luteal phase in IVF cycles is not yet justified.